tbuckley/cabot-search huggingface dataset:
The impacts of initiating regorafenib with reduced dose on treatment outcomes in metastatic colorectal cancer.
Authors: Takeshi Kawakami, Kazuaki Harada, Takatsugu Ogata, Qingjiang Hu, Kunihiro Fushiki, Kotoe Oshima, Shigenori Kadowaki, Hiroya Taniguchi, Kei Muro, Ryota Nakanishi, Koji Ando, Sho Nambara, Takahiro Yamamura, Yasuyuki Kawamoto, Yoshito Komatsu, Eiji Oki, Toshiki Masuishi, Kentaro Yamazaki, Satoshi Yuki
Journal: Journal of Clinical Oncology (2023)

133 Background: Since the results of the ReDOS study were published, starting regorafenib (REG) at a reduced dose is now considered a treatment option for patients with metastatic colorectal cancer (mCRC). However, the impact of starting REG at a reduced dose on treatment outcomes in the real-world setting has not been fully investigated. Methods: We retrospectively analyzed patients who received REG for mCRC at 4 institutions between May 2013 and December 2020. These patients were divided into two groups: those who started REG before (Period A) and after (Period B) the ReDOS study publication (May 2018). The treatment outcomes between Period A and B were compared in this analysis. Results: A total of 573 patients were evaluated (385 in Period A and 188 in Period B, respectively). In Period B, significantly more patients started REG with reduced dose (34.3% vs. 75.5%, p&lt; 0.001). The median time to first dose reduction was 32.0 days [95% CI: 29.1-34.9] in Period A and 61.0 days [95% CI: 33.7-88.9] in Period B, which was significantly longer in Period B (HR = 0.685, p= 0.003). Both any grades and ≥grade3 hand foot skin reaction (HFSR) were significantly less frequent in Period B than in Period A (any grades: 65.5% vs 54.8%, p= 0.017, ≥grade3: 21.3% vs 14.4%, p= 0.054). The median time to onset of any grades HFSR was 16.0 days [95% CI: 13.6-18.4] in Period A and 28.0 days [95% CI: 15.6-40.4] in Period B, which was significantly longer in Period B (HR = 0.738, p= 0.007). The median overall survival was 6.7 months [95% CI: 5.9-7.4] in Period A, and 5.4 month [95% CI: 4.3-6.5] in Period, respectively (HR = 1.105, p= 0.281). The median progression free survival was 2.0 months [95% CI: 1.9-2.1] in Period A and 2.1 months [95% CI: 1.8-2.4] in Period B, respectively (HR = 1.064, p= 0.498). Conclusions: Our results suggest that starting REG at a reduced dose may contribute to reducing the frequency and delaying the onset of HFSR, whereas it may not affect efficacy.
Risks and implications of multiple actionable pathogenic germline variants discovered by panel-based cancer predisposition testing.
Authors: Michael J. Hall, Michelle J McSweeny, Kim Rainey, Hannah Campbell, Chau Nguyen, Catherine Neumann
Journal: Journal of Clinical Oncology (2023)

792 Background: Multi-gene hereditary cancer panels have revolutionized how patients with germline mutations are identified by testing multiple genes at the same time. Despite the availability of panel testing, many patients with a known familial mutation will only undergo single site genetic testing due to limitations in guideline recommendations and insurance coverage. This approach risks a failure to detect additional pathogenic variants and an inappropriate management of cancer risk. In our clinical experience, a subset of patients pursue multigene testing despite a known familial mutation. Our group has identified patients who carry more than one mutation and mutations that would have been missed if the patients had only undergone single site testing. We investigated the patients and families from our risk assessment clinic with multiple familial mutations and determined how medical management may have been changed due to the presence of multiple mutations in family. Methods: The Fox Chase Cancer Center Risk Assessment Program (RAP) Registry was queried to identify patients who carry more than one mutation. Pedigrees of patients and families identified with multiple germline mutations were reviewed. Screening management guidelines were determined from the most recent NCCN guidelines published at the time the patient tested (Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic and Genetic/Familial High-Risk Assessment: Colorectal). The RAP Registry is an IRB approved protocol (IRB 09-831). Results: 70 patients were found to carry at least 2 mutations (excluding patients with biallelic MUTYH mutations) since introducing multi-gene panel testing in 2014. The most common second mutation was the I1307K variant in the APC gene at 20% (14/70). We also identified 20 patients who would have received incomplete genetic risk assessment if they only underwent single site testing and screening management changed in 60% (12/20) of these patients. 35% (7/20) of these patients did not meet NCCN criteria for additional germline testing beyond single site testing. Conclusions: Multi-gene hereditary cancer panels identify patients and families with multiple germline mutations. Patients undergoing single site cascade testing are at risk of receiving inaccurate risk assessment based on incomplete ascertainment of germline cancer risks. Detection of additional actionable mutations will frequently lead to changes in medical management.
Triplets versus doublets in the treatment of right-sided metastatic colorectal cancer in real-world setting: A propensity-score weighting analysis.
Authors: Mariana Gil, Renata D'Alpino Peixoto, Thais Passarini, Maria Cecilia Mathias, Eduardo Dias de Moraes, Jorge Alexandre Canedo, Sabrina Pereira, Larissa Amorim, Gabriel Prolla, Laura Freitas, Matheus Costa e Silva, Carlos G. M. Ferreira, Bruno Lemos Ferrari, Bernardo Garicochea, Rodrigo Dienstmann, Roberto Almeida Gil, Alexandre A. Jácome
Journal: Journal of Clinical Oncology (2023)

55 Background: Right-sided metastatic colorectal cancer (mCRC) has a worse prognosis and the best first-line treatment is still uncertain. The aim of this study was to analyze progression-free survival (PFS) and overall survival (OS) comparing triplet versus doublet backbone chemotherapy in first-line setting for right-sided mCRC. Methods: Retrospective study evaluating 510 patients with mCRC who were treated in a private institution in Brazil from January 2011 to December 2019. Information of 118 patients with right-sided primary tumor was analyzed in this study. Demographic and clinical data were retrieved from electronic medical records. PFS and OS were calculated in months (m) using propensity-score weighting analysis (PSWA) due to expected disparity between the number of patients treated with triplet and doublet regimens. Variables used to balance patient groups were age; metastasectomy; primary tumor resection; bevacizumab use; BRAF and RAS mutation status. Results: The median follow-up was 31 months. Our population was mostly composed of elderly (64%) and female (52%) patients. First-line treatment with triplet backbone chemotherapy was done in 16 patients (14%). Primary tumor resection was done in 14% of the cases, 55% underwent metastasectomy, and 57% received anti-VEGF treatment. BRAF mutation was found in 9% of the patients and RAS mutation in 46%. After PSWA we found a significant better median PFS among patients treated with triplet regimen: 12.7m versus 8.9m compared to those receiving doublet backbone chemotherapy, with a hazard ratio of 0.64 (CI 95%: 0.42 – 0.97); p-value: 0.037. No significant difference was found in OS (29.8m versus 45.5m) between triplet and doublet therapy groups, respectively. Conclusions: In our study we found a significantly better PFS with triplet backbone chemotherapy in first-line setting for right-sided mCRC, encouraging the use of this regimen in treatment-naive selected patients. However, no difference in OS was found, probably due to subsequent treatments. PSWA is an acceptable and needed tool to enable retrospective real world studies involving treatments with expected uneven distribution. More studies are needed to answer the best strategy to target right-sided mCRC, which remains a challenge for oncologists, with unmet needs.
Impact of complete pathological response outcome in Latin American patients with rectal cancer.
Authors: German Calderillo Ruiz, Dr. Consuelo Diaz, Marytere Herrera, Erika Ruiz-Garcia, Sayako Mariana Miyagui-Adame, Berenice Carbajal, Alejandra Albarrán-García, Zugeyth Emireth Murguía-Guzmán
Journal: Journal of Clinical Oncology (2023)

58 Background: Rectal cancer is one of the leading cancer-related causes of death worldwide. Nevertheless, complete pathological response (pCR) to neoadjuvant treatment has been associated with a decrease in local recurrence and distant disease, and therefore an improvement in disease-free survival (DFS) and overall survival (OS). The aim of this study was to evaluate the impact of pCR in DFS and OS Mexican patients with rectal cancer. Methods: Retrospective, observational study. Included patients with rectal adenocarcinoma treated with neoadjuvant chemo-radiotherapy between 1998 and 2021. Statistical analysis: X 2 and t-test, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance p &lt;0.05 bilaterally. Results: A total of 707 patients were included in the analysis. 52.3% were male with a median age of 57 (18 – 86) years. According to clinicopathological features, moderate-grade was the most prevalent at 66%, 38.5% were low-rectum and 32% of patients reported an ACE&lt;10mg/dL. Patients were divided into 2 groups: pCR (n=155) and non-pCR (n=552) for the analysis. According to surgical margins, 89%(n=491) non-pCR-patients reported R0 (p=0.003). Recurrence rate was 12.9%(n=20) versus 35.7%(n=197) in pCR and non-pCR respectively (p&lt;0.001). Regarding DFS analysis, pCR-patients median-DFS was Not Reached (NR), while non-pCR-patients median-DFS was 154 months (p&lt;0.001; HR:0.32, 95%CI:0.20-0.51). At OS analysis, pCR-patients median-OS was NR, non-pCR-patients median-OS was 166 months (p&lt;0.001; HR:0.41,95%CI 0.26-0.65). At DFS-multivariate analysis, location (p&lt;0.001; HR:1.47, 95%CI:1.20-1.80) and rPC (p=0.013; HR:0.48,95%CI:0.27-0.85) remained predictive factors of DFS. At OS-multivariate analysis, ACE (p=0.047; HR:1.37, 95%CI:1.00-1.89) and pCR (p=0.009; HR:0.45, 95%CI:0.24-0.81) remained as predictive factors of OS. Conclusions: The pCR rate in our population is similar of what is reported in the literature. Our study demonstrates that pCR significantly impacts DFS and OS, rectal cancer patients. Total neoadjuvant chemo-radiotherapy, short-scheme-radiotherapy, and immunotherapy in selected populations can achieve doubling the percentage of pCR. [Table: see text]
Real-world outcomes of patients with advanced gastric cancer treated with FOLFIRI.
Authors: Ali Fawaz, Derek Tilley, Hatim Karachiwala
Journal: Journal of Clinical Oncology (2023)

307 Background: Doublet chemotherapy regimens such as 5-fluorouracil and irinotecan (FOLFIRI) appear to be viable first-line treatment options in advanced gastric cancer (AGC). A phase III French intergroup study demonstrated a longer time to treatment failure, improved toxicity profile, and no difference in median OS when using FOLFIRI, compared to epirubicin, cisplatin, and capecitabine (ECX). Purpose: To investigate the real-world efficacy of FOLFIRI in AGC. Methods: Patients diagnosed with AGC in Alberta, Canada from 2012-2020 were identified by the Alberta Cancer Registry. Data points that could not be obtained automatically were obtained by retrospective chart review. Survival was compared by Log-Rank analysis or Cox Regression. Factors associated with FOLFIRI use were determined using logistical regression. Results: A total of 285 patients were analyzed. Eighty-four (29%) patients received FOLFIRI as first-line therapy, 69 received ECX (24%), 82 received CX (29%), 31 received EOX (11%), and 19 received FOLFOX (7%). Thirty-six (12.6%) received a subsequent line of therapy, most commonly FOLFIRI (52.8%). Age, sex, topography (cardia v. non-cardia), or morphology (adenocarcinoma v. signet ring cell v. NOS) did not influence the use of FOLFIRI in the first-line setting. Median overall survival with FOLFIRI was 5.8m vs. 7.4m (p = 0.12) when compared to the patients receiving all other regimens. Conclusions: FOLFIRI had comparable efficacy to other first-line regimens in patients with AGC.
The role of primary tumor resection in synchronous stage IV colorectal cancer: Subgroup analysis.
Authors: Hojung An, Ji Eun Shin, Byoung Yong Shim, Hyunho Kim, Hyung Soon Park, Hyeon-Min Cho, Bong-Hyeon Kye, Ri Na Yoo, Sung Hwan Kim, Jong Hoon Lee, Kang-Moon Lee, Ji Min Lee, Ji-Han Jung
Journal: Journal of Clinical Oncology (2023)

47 Background: The standard treatment for synchronous stage IV colorectal cancer (CRC) is systemic chemotherapy. There have been attempts to conduct elective primary tumor resection (PTR) as an upfront treatment to prevent complications in primary tumor sites, or improve prognosis. However, there are controversies about the role of PTR in stage IV CRC. We investigated the prognostic role of PTR and tried to find subgroups who might get benefit from upfront PTR in this population. Methods: Between 2010 and 2020, 330 patients diagnosed with synchronous stage IV CRC at St. Vincent Hospital in Korea were retrospectively reviewed. We excluded patients underwent PTR and metastasectomy at the same time, PTR for emergencies (perforation, acute bleeding with hemodynamic instability, fistula, and/or obstruction), or received chemoradiotherapy as an initial treatment. Overall survival (OS) was measured from the date of diagnosis until death resulting from any cause or the last censored date during follow-up. OS were calculated using the Kaplan-Meier method, and differences in survival between groups were compared by the log-rank test. Variables with p value &lt;0.05 were included in the Cox regression multivariable model. Results: Total 223 patients were analyzed. Patients were divided into two groups; 45 patients receiving upfront elective PTR (PTR group), and the 178 patients receiving upfront systemic treatment (non-PTR group). Two groups were not different in terms of age ( p = 0.979), ECOG performance status ( p = 0.488), and serum CEA levels ( p = 0.252). However, the PTR group showed lesser number of metastatic organ compared to the non-PTR groups ( p = 0007). The PTR group survived longer than the non-PTR group ( p = 0.015). Multivariate analysis revealed that age≥60 (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.15-2.09; p = 0.004,), CEA≥30 ng/mL (HR, 1.32; 95% CI, 0.99-1.75, p = 0.061), PTR (HR, 0.66; 95% CI, 0.45-0.95; p =0.027), adding targeted agent (HR, 0.71; 95% CI, 0.53-0.96; p = 0.026), and ECOG≥3 (HR, 1.649; 95% CI, 1.15-2.37, p = 0.007) were associated with OS. Subgroup analysis showed that PTR might be beneficial in patients with low CEA (&lt;30 ng/mL, p = 0.032), old age (≥60, p = 0.028), ECOG (≤2, p = 0.006), M1a stage ( p = 0.008), and receiving bevacizumab ( p = 0.016). Conclusions: Upfront PTR was conducted in selected patients with lower number of metastasis, but associated with OS after adjusting other prognostic factors. We suggested that PTR could be an option for patients with low CEA (&lt;30 ng/mL), old age (≥60), ECOG (≤2), M1a stage, or receiving bevacizumab in this population.
Trends in incidence, treatments, and clinical outcomes of cholangiocarcinoma diagnosed in British Columbia, Canada, from 2005 through 2019.
Authors: Mélina Boutin, Jenny Yang, Maria Safro, Helia Jafari, Janine Marie Davies, Sharlene Gill
Journal: Journal of Clinical Oncology (2023)

522 Background: While only accounting for 3% of gastrointestinal malignancies, cholangiocarcinoma (CC) has poor prognosis. New targeted therapies are on the horizon and understanding the potential size of the population eligible for such therapies is of importance. Contemporary incidence and outcomes in Canada have not been studied. Methods: Patients diagnosed with CC between 2005-2019 in British Columbia were identified using the BC Cancer Registry. Patient characteristics, treatments received and outcomes were collected and analyzed. Results: A total of 1520 patients were identified. Median age at diagnosis was 69 (interquartile 61-76) and 52% were female, 594 patients presented with localized disease (39%) of whom 416 had disease recurrence. The proportion of intrahepatic CC (ICC) rose from 17% in 2005-2009 to 44% in 2015-2019 while the incidence of extrahepatic (ECC) and gallbladder (GB) cancers followed populational trends. More patients with ICC had stage IV cancer at the time of diagnosis (64% vs 43% for ECC and 45% for GB, p&lt;0.01). Treatments received are shown in the table. Among 1086 patients with recurrent or metastatic disease, 54% and 14% respectively received first- and second-line chemotherapy. Overall survival (OS) was 13.7 months [HR 0.43 (95% CI 0.37-0.49)] with 1 line of treatment and 21.3 months with 2 lines [HR 0.30 (95% CI 0.24-0.37)], compared to 4.8 months with best supportive care. On multivariate analysis, ECOG, first and second-line treatment and liver-directed therapy remained associated with improved outcomes while tumor site or time period did not. Conclusions: The incidence of CC is rising and most patients present with advanced disease. Treatment attrition is high and few patients receive second line therapies. The outcomes of patients receiving first line, second line and liver-directed therapies are significantly better than those receiving supportive care only. Understanding contemporary trends in presentation and treatment patterns is essential as we consider strategies to improve implementation and access of emerging novel therapies in this setting. [Table: see text]
SEAMARK: Randomized phase 2 study of pembrolizumab + encorafenib + cetuximab vs pembrolizumab alone for first-line treatment of BRAF V600E–mutant microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC).
Authors: Scott Kopetz, Tanios S. Bekaii-Saab, Takayuki Yoshino, Chin-Hee Chung, Xiaosong Zhang, Josep Tabernero
Journal: Journal of Clinical Oncology (2023)

TPS268 Background: Among patients with MSI-H/dMMR CRC, BRAF mutations occur in approximately 30%. MSI-H/dMMR and BRAF mutations are both associated with poor prognosis; in patients who have both biomarkers, poor prognosis is thought to be driven by the BRAF mutation. Pembrolizumab is indicated for the treatment of patients with MSI-H/dMMR unresectable or metastatic CRC (mCRC). The BRAF inhibitor encorafenib, in combination with cetuximab, an anti-EGFR antibody, is indicated for previously treated patients with BRAF V600E-mutant mCRC. Currently, there are no first-line treatment options indicated specifically for patients with both MSI-H/dMMR and BRAF V600E-mutant mCRC. To assess the safety and efficacy of combining pembrolizumab with encorafenib + cetuximab, the SEAMARK study will evaluate this combination vs pembrolizumab alone in patients with previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC. Methods: SEAMARK (NCT05217446) is an open-label, multicenter, randomized, phase 2 study. Approximately 104 patients (randomized 1:1; stratified by Eastern Cooperative Oncology Group Performance Status [ECOG PS] 0 vs 1) will receive either pembrolizumab + encorafenib + cetuximab or pembrolizumab. Enrolled patients must be aged ≥16 or ≥18 years (per country-specific regulations) and have previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC; measurable disease (Response Evaluation Criteria in Solid Tumors 1.1); ECOG PS 0 or 1; and adequate bone marrow, hepatic, and renal function. Patients who received prior treatment with BRAF/EGFR inhibitors or immune checkpoint inhibitors, or who have brain metastases (unless radiologically stable) or RAS mutation (or unknown RAS status), will be excluded. The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include safety and tolerability, overall survival, objective response rate, duration of response, and quality of life. Enrollment started in July 2022. Clinical trial information: NCT05217446 .
Impact of COVID-19 pandemic on diagnosis, staging, and outcomes of patients with early-onset colorectal cancer.
Authors: Daniel Martinez-Perez, David Viñal, Jose Ángel García Cuesta, Antonio Rueda-Lara, Iciar Ruiz-Gutierrez, Diego Jiménez-Bou, Jesus Peña-Lopez, Gema Martin-Montalvo, Maria Alameda-Guijarro, Laura Gutiérrez-Sainz, Antonio Barbachano, Javier Rodriguez-Cobos, Pilar Bustamante-Madrid, Maria Jesús Larriba, Asuncion Fernandez-Barral, Aurora Burgos, Maria Isabel Prieto-Nieto, Laura Guerra Pastrian, Jose Manuel Gonzalez-Sancho, Nuria Rodriguez Salas
Journal: Journal of Clinical Oncology (2023)

15 Background: Although we seem to be recovering from COVID-19, we are now facing the long-term consequence of the pandemic on vulnerable subgroup of patients such as patients with early-onset colorectal cancer (EOCRC). We aim to study how the COVID-19 pandemic affected the diagnosis and clinic-pathological characteristics, treatment and outcomes of patients with EOCRC. Methods: This is an observational retrospective study including patients with EOCRC diagnosed between September 2016 and August 2021 at Hospital Universitario La Paz, Madrid, Spain. Two cohorts were stablished: before and after March 14, 2020, the day of the first lockdown in Spain. Results: A total of 1409 patients with CRC were included. Of those, 5,2% were EOCRC (n=75). Fifty-five (73%) and 20 (27%) were diagnosed pre, and post pandemic. The rate of EOCRC diagnosis per month was 1,8 and 1,1 in the pre and postpandemic group, respectively. Fifty percent of patients in the postpandemic group were diagnosed with metastatic disease, while only 29% had stage IV at diagnosis in the prepandemic subgroup (P = 0,09). High tumor budding, surgical margins affected, lymphovascular, and perineural invasion were also pathological features more observed in the postpandemic subgroup, although results are not statistically significant. The differences between both groups are depicted. After a median follow-up of 23 months (33 and 14 months in the pre and postpandemic group, respectively), 11 patients have died (15%). Median overall survival (OS) was not reached in either group. At 12 months, 94% and 89% of patients were alive in the pre and postpandemic group, respectively. Conclusions: COVID-19 has influenced the diagnosis and staging of patients with EOCRC. Long-term follow-up is needed to assess the survival in this population. The role of primary care in the diagnosis and early referral of these patients is, more than ever, crucial. [Table: see text]